The issue of hair growth or hair loss disorders has persistently bothered men, women and children of all ages. There are various reasons as to the causes of such disorders including aging, diseases and medical treatments. To address the various causes of hair disorders, several solutions for the reduction of hair loss and stimulation of hair growth are available depending on the causes in each individual's case. Some of these solutions may include dietary supplements, pharmaceutical drugs or even hair transplantation. The drawbacks to some of these solutions are the occurrence of side effects or that their effects fall short of the ultimate goal of mitigating hair disorders, e.g., minoxidil tends to produce fine hairs instead of mature hairs; finasteride tends to slow down baldness instead of promoting hair growth. Hence, there is a need for more and better drugs for the targeted treatment of hair disorders.
To create new drugs, various bioengineered scaffolds have been constructed to mimic the cellular structure of the scalp or other parts of the body, in particular the epithelial-mesenchymal interactions in the hair follicle (HF), for pre-clinical assessment of these new drugs.
Previous efforts include creating a layered scaffold that comprises of a pseudodermis (a collagen base mixed with human dermal fibroblasts (HDF)). Later, these pseudodermis may be covered with various cells and matrix mixtures which contained basement membranes and extracellular components. For example, covering with a first layer containing Matrigel™ mixed with dermal papilla fibroblasts (DPC) on top of the pseudodermis followed by another layer containing outer root sheath keratinocytes (ORSK).
Another similar construct known as the mixed layered system comprises of covering the pseudodermis with a single matrix containing Matrigel™, DPC and ORSK rather than having them in separate layers.
The problem with such layered scaffolds is that they have to be subjected to histochemical stainings for accurate analysis. It is also known that the construction of such layered structures, which are very laborious and time consuming resulting in low throughput, tend to result in disappointing structural appearances that do not mimic actual hair follicles intended for use in pre-clinical investigations.
One other technique may involve seeding the cell mixture onto membranes where the cells are able to aggregate, proliferate, or differentiate and eventually detach off the membranes. Spheroid constructs with a mixture of dermal papilla and ORSK have also been fabricated by extruding the cells (mixed with collagen) into a gelling bath. Likewise, both of these methods and construct configurations suffer from the abovementioned issues, in particular lacking the HF architecture and proper orientation of DPC and keratinocytes. Moreover, these structures cannot be easily analyzed due to the need for fixation, to be sectioned and histochemically stained before visualizations of the structures are enabled.
Accordingly, there is a need for engineered scaffolds constructed in a manner such that it allows for the epithelial-mesenchymal interactions, encourage cell proliferation and prevent apoptosis.
Accordingly, there is a need for a method of constructing said engineered scaffolds that is less labor intensive and easily reproducible to achieve higher throughput.
There is a need to provide a testing platform for drugs used in hair treatment that overcomes, or at least ameliorates, one or more of the disadvantages described above.